The therapeutic efficacy of nitric oxide (NO) has been demonstrated across many different treatment methods. For example, NO has cytotoxic, antiviral, anti-inflammatory, and vasodilator properties. Nitric oxide also has been shown to dramatically reduce thrombocyte and fibrin aggregation/adhesion and smooth muscle cell hyperplasia while promoting endothelial cell growth (Cha et al., Haematologia (Budap), 30(2): 97-106 (2000); Lowson et al., Anesth. Analg., 89(6): 1360-1365 (1999); Riddel et al., Vitam. Horm., 57: 25-48 (1999); Gries et al., Circulation, 97(15): 1481-1487 (1998); and Liischer, Schweiz Med. Wochenschr., 121(51-52): 1913-1922 (1991)). Wounds are known to be deficient in nitric oxide, and as a result, application of NO has been shown to also have beneficial effects on wound healing by, e.g., promoting angiogenesis and tissue remodeling, since NO plays a role in collagen formation. See, e.g., Cortivo et al., Nanomedicine, 5: 641-656 (2010).
Diabetics often suffer from chronic impaired healing, and attempts to use NO therapy have been made. For instance, NO derived from the NO donor molsidomine has been shown to enhance healing in patients with diabetes (Witte et al., Br. J. Surg., 89: 1594-1601 (2002)). S-nitrosothiols have been used as NO donors in polymer blends comprising poly(vinyl methyl ether-co-maleic anhydride) (PVMMA) and poly(N-vinyl-2-pyrrolidone) (PVP) (Li et al., Molecular Pharmaceutics, 7(1): 254-266 (2010)).
However, the delivery of nitric oxide in a stable, nontoxic, and prolonged manner remains a concern. Thus, there remains a desire to provide alternative treatments to improve wound healing and promote angiogenesis with nitric oxide in a manner that is stable, biocompatible, and preferably, bioabsorbable.